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Administrative data

Description of key information

Respiratory tract:
- human: study with 9 human volunteers exposed for 1 hour : NOAEC = 216 ppm (Stewart et al., 1968)
Eye:
- rabbit: irritating (Wolf et al., 1956)
Skin:
- rabbit: irritating (Wolf et al., 1956; Spencer et al., 1942; Futamura et al., 2009)

Key value for chemical safety assessment

Additional information

In the UK RAR (June 2008) the data on irritation and corrosivity were summarized as follows (the references are given in brackets):

 

Summary of irritation

The quality of information on the skin irritation potential of liquid styrene is poor, particularly in relation to the consequences of a single application. The available data suggest that a single exposure is not significantly irritating, but that repeated exposure does cause irritation (Spencer et al., 1942; Wolf et al., 1956; Berode et al., 1985).

 

The available evidence suggests that liquid styrene can produce eye irritation (Wolf et al., 1956). Exposure to airborne styrene vapour can also cause eye irritation (Spencer et al., 1942; Wolf et al., 1956). Concentrations of 375 ppm and above are clearly irritating. Exposures of up to approximately 216 ppm for one hour were without effect. Although slight eye “irritation” was reported by subjects following exposure to 100 ppm styrene for 7 hours, absence of effects in the same study at 216 ppm for 1 hour exposure suggests that the effect with longer exposure was not primary irritation, but perhaps eye dryness or some similar sensation. NOAEC values of 216 ppm for 1 hour and of 100 ppm for 7 hours are therefore identified for risk characterisation purposes (Stewart et al., 1968).

 

It is clear that exposures to airborne styrene can cause respiratory tract (nasal) irritation. No effects were seen at 100 ppm for 1 hour or 7 hours and only one subject out of nine reported nasal irritation at 216 ppm for 1 hour, suggesting little or no significant irritation at this concentration. Nasal irritation was more evident at 375 ppm for 1 hour and above, in several studies. NOAEC values of 216 ppm for 1 hour and of 100 ppm for 7 hours are therefore identified for risk characterisation purposes (Stewart et al., 1968).

 

Corrosivity

The studies in animals and humans indicate that styrene is not corrosive.

 

A literature search from 1998 to January 2010 overlapping the date of the UK RAR (June 2008) was conducted. Overall, this did not lead to a modification of the conclusions reached by the UK RAR and reinforced some of the aspects elaborated above.

 

The potential for skin irritation is supported by Futamura et al. (2009) measuring microvascular leakage after dermal application to rats. Microvasular leakage was observed after topical application of formalin and styrene as well as of other aromatic solvents (xylene, toluene, benzene, ethylbenzene). No such effects were reported after application of aliphatic chemicals (hexane, heptane, cylohexane) or ethanol, methanol, acetone, or diethyl ether.

 

Lanosa et al. (2010) demonstrated that sensory respiratory irritation measured by plethysmography depends on metabolic activation of styrene. Mice were exposed to 75 ppm styrene. After pretreatment with the CYP inhibitor metyrapone the plethismographic response was massively diminished. They also reported that 5-phenyl-1-pentyne completely abolished the response. Irritation was mediated by the TRPA1 receptor that has been shown to mediate respiratory irritation responses for several oxidants and electrophiles. In contrast to wild type mice, TRPA1 knock out mice did not response to sensory irritation by 75 ppm styrene.

 

Justification for classification or non-classification

Taken together, in a weight of evidence approach, the present data for the test substance identify styrene to cause irritation of the skin, of the eyes and of the respiratory tract.

Therefore, styrene fulfils the requirements to be classified as Category 2, H315 for skin irritation according to GHS-CLP criteria (1272/2008/EC) and as Xi, R38 according to EU-DSD criteria (67/548/EEC).

With regard to the eye, styrene fulfills the requirements to be classified as Category 2A, H319 for eye irritation according to GHS-CLP criteria (1272/2008/EC) and as Xi, R36 according to EU-DSD criteria (67/548/EEC).

With regard to the respiratory tract, styrene fulfils the requirements to be classified as STOT single exposure Category 3, H335 for respiratory irritation according to GHS-CLP criteria (1272/2008/EC) and as Xi, R37 according to EU-DSD criteria (67/548/EEC).

The classification for skin and eye irritation is in accordance with the current legal classification laid down in Annex I of DSD-67/548/EEC (ATP 19) and Annex VI of CLP-1272/2008/EC, respectively.